The name of Canicattì is of Arabic origin, from خندق الطين Khandaq al-ṭīn, meaning 'clay ditch'.

In 1448 the fief of Canicattì was ceded by Antonio Palmieri, who was heirless, to his nephew Andrea De Crescenzio, who obtained by king John II of Aragon the Licentia populandi, i.e. the permission to enlarge the fief's boundaries, increase its population and administer justice.

Under Andrea De Crescenzio Canicattì was a rural community including some 1000/1500 inhabitants, living in the upper part of the town.

In 1943 it was the seat of the Canicattì massacre, in which American troops killed several Italian civilians who were looting a factory and refusing to disperse despite warnings.

Canicattì station is an important hub for local rail transport and, until 2011, it was served by express trains linking Agrigento with Rome, Milan and Turin.